Methods and pharmaceutical compositions for the cardioprotection

The present invention relates to methods and pharmaceutical compositions for cardioprotection of subjects who experienced a myocardial infarction. In particular, the present invention relates to a ligand of the sonic hedgehog signaling pathway for use in the cardioprotection of a subject who experienced a myocardial infarction

Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils

Rationale: Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder. Objective: Here, we use single atrial myofibrils and fast solution switching techniques to directly investigate the impact of cAF on myofilament mechanical function eliminating changes induced by the arrhythmia in atrial myocytes membranes and extracellular components. Remodeling of sarcomere proteins potentially related to the observed mechanical changes is also investigated. Methods and Results: Myofibrils were isolated from atrial samples of 15 patients in sinus rhythm and 16 patients with cAF. Active tension changes following fast increase and decrease in [Ca2+] and the sarcomere length\u2013passive tension relation were determined in the 2 groups of myofibrils. Compared to sinus rhythm myofibrils, cAF myofibrils showed (1) a reduction in maximum tension and in the rates of tension activation and relaxation; (2) an increase in myofilament Ca2+ sensitivity; (3) a reduction in myofibril passive tension. The slow \u3b2-myosin heavy chain isoform and the more compliant titin isoform N2BA were up regulated in cAF myofibrils. Phosphorylation of multiple myofilament proteins was increased in cAF as compared to sinus rhythm atrial myocardium. Conclusions: Alterations in active and passive tension generation at the sarcomere level, explained by translational and post-translational changes of multiple myofilament proteins, are part of the contractile dysfunction of human cAF and may contribute to the self-perpetuation of the arrhythmia and the development of atrial dilatation

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas

Background: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. Methods: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non- BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. Results: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. Conclusion: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitorsThis study was funded by the Fondo de Investigacio´n Sanitaria (FIS), Instituto de Salud Carlos III (grants CP07/00113 and PS09/01094

Remote sensing of lunar aureole with a sky camera: Adding information in the nocturnal retrieval of aerosol properties with GRASP code

The use of sky cameras for nocturnal aerosol characterization is discussed in this study. Two sky cameras are configured to take High Dynamic Range (HDR) images at Granada and Valladolid (Spain). Some properties of the cameras, like effective wavelengths, sky coordinates of each pixel and pixel sensitivity, are characterized. After that, normalized camera radiances at lunar almucantar points (up to 20° in azimuth from the Moon) are obtained at three effective wavelengths from the HDR images. These normalized radiances are compared in different case studies to simulations fed with AERONET aerosol information, giving satisfactory results. The obtained uncertainty of normalized camera radiances is around 10% at 533 nm and 608 nm and 14% for 469 nm. Normalized camera radiances and six spectral aerosol optical depth values (obtained from lunar photometry) are used as input in GRASP code (Generalized Retrieval of Aerosol and Surface Properties) to retrieve aerosol properties for a dust episode over Valladolid. The retrieved aerosol properties (refractive indices, fraction of spherical particles and size distribution parameters) are in agreement with the nearest diurnal AERONET products. The calculated GRASP retrieval at night time shows an increase in coarse mode concentration along the night, while fine mode properties remained constant.This work was supported by the Andalusia Regional Government (project P12-RNM-2409) and by the “Consejería de Educación, Junta de Castilla y León” (project VA100U14).Spanish Ministry of Economy and Competitiveness and FEDER funds under the projects CGL2013-45410-R, CMT2015-66742-R, CGL2016-81092-R.“Juan de la Cierva-Formación” program (FJCI-2014-22052).European Union's Horizon 2020 research and innovation programme through project ACTRIS-2 (grant agreement No 654109)

Expression of Matrix Metalloproteinases and Their Inhibitors in Squamous Cell Carcinoma of the Tonsil and Their Clinical Significance

ObjectivesTo investigate expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in squamous cell carcinoma of the tonsil and to correlate expression profiles with clinicopathological characteristics.MethodsParaffin blocks were obtained from 45 tonsil squamous cell carcinoma (SCC) patients, who underwent surgery as an initial treatment between 1994 and 2004, and from 20 normal controls. Expressions of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 were investigated immunohistochemically.ResultsThe expressions of MMPs (except MMP-2) and TIMPs were found to be significantly different in tonsil SCC and normal control tissues. Furthermore, MMP-13 expression was found to be correlated with tumor invasion (P=0.05), and the expressions of MMP-9 and TIMP-1 with nodal metastasis (P=0.048, 0.031). No relation was found between MMP or TIMP expression and recurrence. However, MMP-9 expression was found to be significantly associated with 5-year survival in tonsil SCC patients by multivariate analysis (hazard ratio, 3.853; P=0.013).ConclusionSignificant overexpressions of multiple MMPs and TIMPs were found in tonsil SCC tissues. Furthermore, our findings suggest that MMP-9 expression might be a useful prognostic factor

Transmural variations in gene expression of stretch-modulated proteins in the rat left ventricle

The properties of left ventricular cardiac myocytes vary transmurally. This may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. We tested the hypothesis that within the rat left ventricle there are transmural differences in the expression of genes for proteins that are involved in mechanosensitive pathways and in associated physiological responses. Real time reverse transcription polymerase chain reaction was used to measure messenger RNA (mRNA) levels of selected targets in sub-epicardial (EPI) and sub-endocardial (ENDO) myocardium. Carbon fibres were attached to single myocytes to stretch them and to record contractility. We observed that the slow positive inotropic response to stretch was not different between EPI and ENDO myocytes and consistent with this, that the mRNA expression of two proteins implicated in the slow response, non-specific cationic mechanosensitive channels (TRPC-1) and Na/H exchanger, were not different. However, mRNA levels of other targets, e.g. the mechanosensitive K+ channel TREK-1, Brain Natriuretic Peptide and Endothelin-1 receptor B, were significantly greater in ENDO than EPI. No targets had significantly greater mRNA levels in EPI than ENDO. On the basis of these findings, we suggest that the response of the ventricle to stretch will depend upon both the regional differences in stimuli and the relative expression of the mechanosensitive targets and that generally, stretch sensitivity is predicted to be greater in ENDO

Retrieval of aerosol profiles combining sunphotometer and ceilometer measurements in GRASP code

This is a preprint version of article accepted "Roman, A.; et al. Retrieval of aerosol profiles combining sunphotometer and ceilometer measurements in GRASP code. Atmospheric Research, 204: 161-177 (2018). DOI: https://doi.org/10.1016./j.atmosres.2018.01.021".In this paper we present an approach for the profiling of aerosol microphysical and optical properties combining ceilometer and sun/sky photometer measurements in the GRASP code (General Retrieval of Aerosol and Surface Properties). For this objective, GRASP is used with sun/sky photometer measurements of aerosol optical depth (AOD) and sky radiances, both at four wavelengths and obtained from AErosol RObotic NETwork (AERONET), and ceilometer measurements of range corrected signal (RCS) at 1064 nm. A sensitivity study with synthetic data evidences the capability of the method to retrieve aerosol properties such as size distribution and profiles of volume concentration (VC), especially for coarse particles. Aerosol properties obtained by the mentioned method are compared with airborne in-situ measurements acquired during two flights over Granada (Spain) within the framework of ChArMEx/ADRIMED (Chemistry-Aerosol Mediterranean Experiment/Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region) 2013 campaign. The retrieved aerosol VC profiles agree well with the airborne measurements, showing a mean bias error (MBE) and a mean absolute bias error (MABE) of 0.3 µm3/cm3 (12%) and 5.8 µm3/cm3 (25%), respectively. The differences between retrieved VC and airborne in-situ measurements are within the uncertainty of GRASP retrievals. In addition, the retrieved VC at 2500 m a.s.l. is shown and compared with in-situ measurements obtained during summer 2016 at a high-atitude mountain station in the framework of the SLOPE I campaign (Sierra Nevada Lidar AerOsol Profiling Experiment). VC from GRASP presents high correlation (r=0.91) with the in-situ measurements, but overestimates them, MBE and MABE being equal to 23% and 43%.This work was supported by the Andalusia Regional Government (project P12-RNM-2409) and by the “Consejería de Educación” of “Junta de Castilla y León” (project VA100U14); the Spanish Ministry of Economy and Competitiveness under the projects, CMT2015-66742-R, CGL2016-81092-R and “Juan de la Cierva-Formación” program (FJCI-2014-22052); and the European Union's Horizon 2020 research and innovation programme through project ACTRIS-2 (grant agreement no 654109) and the Marie Curie Rise action GRASP-ACE (grant agreement no 778349). The authors thankfully acknowledge the FEDER program for the instrumentation used in this work. COST Action TOPROF (ES1303), supported by COST (European Cooperation in Science and Technology), is also acknowledged